N-substituted phthalimide compound and method for obtaining the same



United States Patent N-SUBSTITUTED PHTHALITMIDE COMPOUND AND METHOD FOROBTAINING THE SAME Loren M. Long, Grosse Pointe Woods, and Helen I.Scholl, River Rouge, Mich., assignors to Parke, Davis & Company,Detroit, Mich., a corporation of Michigan No Drawing. ApplicationFebruary 12, 1952, Serial No. 271,281

1 Claim. (Cl. 260-326) This invention relates to an N-substitutedphthalimide compound manifesting chemotherapeutic activity and to aprocess for preparing the same. More particularly, the invention relatesto the production of N-methyl tetrahydrophthalimide, having the formula,

In accordance with the invention, the above product is produced byreacting tetrahydrophthalic acid or tetrahydrophthalic anhydride with atleast one chemical equivalent of methylamine and heating theintermediate product so produced at a temperature between about 100 and300 C. In carrying out the initial portion of the process, it isadvantageous to employ a solvent such as water, a lower aliphaticalcohol or a mixture of the same. The relative quantities of thereactants are not particularly critical, but from the standpoint ofeconomy at least one and preferably several equivalents of methylamineshould be used for each equivalent of the tetrahydropthalic acid oranhydride. The intermediate products differ depending on which startingmaterial is employed, as well as on the amount of methylamine used. Whenthe tetrahydrophthalic anhydride is used with one equivalent ofmethylamine, the intermediate is the half amide While, if two or moreequivalents of methylamine are used, the intermediate product is themethylamine salt of the half amide 2,698,850 Patented Jan. 4, 1955 "iceof tetrahydrophthalic acid. In the case where tetrahydrophthalic acid isused as the starting material, the intermediate product is either themonoor (ii-methylamine salt of tetrahydrophthalic acid. As statedpreviously, these intermediate products are converted to the desiredN-methyl tetrahydrophthalimide by heating them at a temperature betweenabout 100 and 300 C. The preferred temperature for this conversion isinthe neighborhood of 200 to 250 C. at which temperature the reaction iscomplete in about one hour.

The product of the invention possesses valuable therapeutic propertiesand is particularly useful in the treatment of the petit mal type ofepilepsy.

lThe invention is illustrated by the following examp es:

Example 1 10 g. of tetrahydrophthalic anhydride is dissolved in 10 cc.of water containing 40 per cent by weight of methylamine at roomtemperature. The water is distilled from the reaction mixture and theresidue heated at 200 to 250 C. for approximately one hour. The residueis distilled in vacuo to obtain the desired N-methyltetrahydrophthalimide; B. P. 151-3 C. at 10 mm.; M. P. 7 C.; yield 93%.

Example 2 References Cited in the file of this patent UNITED STATESPATENTS Tawney Oct. 3, 1950 OTHER REFERENCES Chem. Abst., vol. 44, p.1223c, citing Travis et al., J. Econ. EntomoL, 42, pp. 686 94 (1949).

Beilstein: Handbuch der Organischen Chemie, vol. 21, p. 461, citingFreund et al., Berichte 3], 1945.

